scholarly journals Identifying a disease-specific renin–angiotensin–aldosterone system fingerprint in patients with primary adrenal insufficiency

2019 ◽  
Vol 181 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Peter Wolf ◽  
Johanna Mayr ◽  
Hannes Beiglböck ◽  
Paul Fellinger ◽  
Yvonne Winhofer ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Risk ◽  
Plasma Renin Activity ◽  
Adrenal Insufficiency ◽  
Replacement Therapy ◽  
Plasma Renin ◽  
Renin Activity ◽  
Mean Blood Pressure ◽  
Ang Ii ◽  
Primary Adrenal Insufficiency

Background In patients suffering from primary adrenal insufficiency (AI) mortality is increased despite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, mainly due to an increased cardiovascular risk. Since activation of the renin–angiotensin–aldosterone system (RAAS) plays an important role in the modulation of cardiovascular risk factors, we performed in-depth characterization of the RAAS activity. Methods Eight patients with primary AI (female = 5; age: 56 ± 21 years; BMI: 22.8 ± 2 kg/m2; mean blood pressure: 140/83 mmHg; hydrocortisone dose: 21.9 ± 5 mg/day; fludrocortisone dose: 0.061 ± 0.03 mg/day) and eight matched healthy volunteers (female = 5; age: 52 ± 21 years; BMI: 25.2 ± 4 kg/m2; mean blood pressure:135/84 mmHg) were included in a cross-sectional case–control study. Angiotensin metabolite profiles (RAS-fingerprints) were performed by liquid chromatography mass spectrometry. Results In patients suffering from primary AI, RAAS activity was highly increased with elevated concentrations of renin concentration (P = 0.027), angiotensin (Ang) I (P = 0.022), Ang II (P = 0.032), Ang 1-7 and Ang 1-5. As expected, aldosterone was not detectable in the majority of AI patients, resulting in a profoundly suppressed aldosterone-to-AngII ratio (AA2 ratio, P = 0.003) compared to controls. PRA-S, the angiotensin-based marker for plasma renin activity, correlated with plasma renin activity (r = 0.983; P < 0.01) and plasma renin concentration (r = 0.985; P < 0.001) and was significantly increased in AI patients. Conclusions AI is associated with a unique RAAS profile characterized by the absence of aldosterone despite strongly elevated levels of angiotensin metabolites, including the potent vasoconstrictor AngII. Despite state-of-the-art hormone replacement therapy, the RAAS remains hyperactivated. The contribution of Ang II in cardiovascular diseases in AI patients as well as a potential role for providing useful complementary information at diagnosis and follow up of AI should be investigated in future trials.

Angiotensin II Blockade before and after Marked Sodium Depletion in Patients with Hypertension

1978 ◽  
Vol 54 (1) ◽  
pp. 75-83 ◽  
Author(s):  
P. Van Hoogdalem ◽  
A. J. M. Donker ◽  
F. H. H. Leenen
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Sodium Intake ◽  
Plasma Renin ◽  
Hypotensive Effect ◽  
Renin Activity ◽  
Mean Blood Pressure ◽  
Sodium Depletion ◽  
Before And After

1. Angiotensin II blockade before and after marked sodium depletion in patients with hypertension [unilateral renovascular (eight), bilateral renovascular (four) and essential (four)] was performed by intravenous administration of the angiotensin II antagonist Sar1-Ala8-angiotensin II (saralasin). 2. On normal sodium intake, saralasin decreased mean blood pressure by 8 mmHg in the unilateral renovascular group, by 6 mmHg in the bilateral renovascular group and increased it by 3 mmHg in the essential hypertensive group. After sodium depletion saralasin decreased mean blood pressure by 33 mmHg, 35 mmHg and 18 mmHg respectively. The saralasin-induced decrease in blood pressure significantly correlated with the log of the initial plasma renin activity. 3. Saralasin infusion decreased effective renal plasma flow (ERPF) in all three hypertension subgroups, both on normal sodium intake and after sodium depletion. Glomerular filtration rate decreased in direct relation to the hypotensive effect of saralasin but ERPF showed this relationship only after sodium depletion. On normal sodium intake saralasin increased filtration fraction by 17%, but decreased it by 7% after sodium depletion. 4. It is concluded that the hypotensive action of saralasin closely correlates with the value of circulating plasma renin activity, apparently independent of the aetiology of the hypertension. The decrease in ERPF during saralasin infusion in the patients on normal sodium intake seems mainly related to the agonistic activity of saralasin, but that after sodium depletion to the hypotensive effect of saralasin.

Renin, Blood Volume and Response to Saralasin in Patients on Chronic Haemodialysis: Evidence against Volume- and Renin-‘Dependent’ Hypertension

1978 ◽  
Vol 54 (3) ◽  
pp. 305-312
Author(s):  
B. P. McGrath ◽  
J. G. G. Ledingham
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Blood Volume ◽  
Plasma Renin ◽  
Renin Activity ◽  
Mean Blood Pressure ◽  
Dietary Sodium ◽  
Chronic Haemodialysis ◽  
Plasma Angiotensin

1. No significant relationship was found between blood pressure and blood volume, sulphate space or plasma angiotensin II concentration in 59 non-nephrectomized haemodialysis patients, of whom 42 were hypertensive. Supine mean blood pressure was only weakly correlated with plasma renin activity and the correlation was not improved when blood pressure was related to expressions combining renin and volume. 2. Changes in supine mean blood pressure during saralasin infusion were related to pre-infusion plasma renin activity (P < 0·001) or plasma angiotensin II (P < 0·02) but also to blood volume (P < 0·001) or sulphate space (P < 0·001). A fall of more than 10% in mean blood pressure during saralasin infusion was observed in only 12 patients (one normotensive), in five of whom there was evidence of volume depletion. 3. Thirteen patients (nine hypertensive) were studied at two levels of dietary sodium: 100 mmol/day and < 20 mmol/day. Supine mean blood pressure in hypertensive patients was lower during the period of higher salt intake despite increased volumes. 4. Hypertension in haemodialysis patients cannot be adequately explained by abnormalities either in volume homeostasis and/or in the renin—angiotensin system.

Mechanism of the Haemodynamic Interaction between Atenolol, a Cardioselective β-Adrenoreceptor-Blocking Agent, and Chlorthalidone in Hypertensive Patients

1979 ◽  
Vol 57 (s5) ◽  
pp. 363s-365s
Author(s):  
M. Velasco ◽  
J. Guevara ◽  
J. Morillo ◽  
A. Ramírez ◽  
A. Urbina-Quintana ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Plasma Renin Activity ◽  
Vascular Resistance ◽  
Plasma Renin ◽  
Renin Activity ◽  
Mean Blood Pressure ◽  
Time Interval ◽  
Calf Blood Flow

1. The effect of the cardioselective β-adrenoreceptor antagonist atenolol on blood pressure, heart rate, systolic time interval, limb blood flow and limb vascular resistance was studied, both when the drug was used by itself, and also when combined with chlorthalidone. Plasma renin activity and plasma atenolol concentration were also measured. 2. After the administration of atenolol alone, there was a decrease in mean blood pressure from 131·8 ± sem 2·88 mmHg to 119·0 ± 4·05 mmHg (P &lt; 0·001), in heart rate from 76·4 ± 3·58 beats/min to 57·0 ± 2·55 beats/min (P &lt; 0·001), in calf blood flow from 9·23 ± 1·39 ml min−1100 g−1 to 5·05 ± 0·89 ml min−1 100 g−1 (P &lt; 0·001), and an increase in calf vascular resistance from 16·54 ± 1·90 (mmHg min−1100 g−1)/ml to 28·53 ± 3·40 (mmHg min−1 100 g−1)/ml) (P &lt; 0·005). Atenolol did not alter the pre-ejection period index significantly (P &gt; 0·1). In atenolol-treated patients, upon addition of chlorthalidone there was a further decrease in mean blood pressure from 119·0 ± 4·05 mmHg to 105·9 ± 4·12 mmHg (P &lt; 0·001). There was no further significant alteration in heart rate, pre-ejection period index, calf blood flow or calf vascular resistance. 3. Atenolol decreased plasma renin activity from 4·69 ± 0·87 to 2·85 ± 0·68 ng h−1 ml−1 (P &lt; 0·05), and the addition of chlorthalidone increased it from 2·85 ± 0·68 to 3·81 ± 0·98 ng h−1 ml−1 (P &lt; 0·05). 4. There was a 7·8 fold-interindividual variability in the relationship between plasma atenolol concentration and the dose of atenolol after a single oral dose of 100 mg of the drug.

Effects of Indomethacin in Rabbit Renovascular Hypertension

1976 ◽  
Vol 51 (s3) ◽  
pp. 249s-251s
Author(s):  
C. G. Strong ◽  
J. C. Romero
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Plasma Renin Activity ◽  
Prostaglandin E2 ◽  
Renovascular Hypertension ◽  
Plasma Renin ◽  
Renin Activity ◽  
Mean Blood Pressure ◽  
Plasma Creatinine ◽  
Goldblatt Hypertension

1. Indomethacin inhibits prostaglandin synthesis and interferes with renin release; these effects were studied in rabbit renovascular hypertension. 2. Ten intravenous inject ons (3 mg day—1 kg—1 after two initial doses of 9 mg/kg) of indomethacin were given daily to ten normal rabbits, ten rabbits with two-kidney Goldblatt hypertension (2KH), and ten rabbits with one-kidney Goldblatt hypertension (1KH). Twelve appropriate control rabbits received diluent phosphate buffer without indomethacin. Plasma renin activity and plasma prostaglandin E2 were measured by radioimmunoassay. 3. In the normal group, indomethacin significantly decreased plasma prostaglandin E2 (1·15 to 0·2 ng/ml, sem 0·2; P < 0·01) and plasma renin activity (20 to 3 ng h—1 ml—1, sem 1, P < 0·01). Plasma creatinine increased slightly but the mean blood pressure was not significantly changed by indomethacin. 4. Six of ten rabbits with 2KH showed results similar to those in the normal rabbits. In four of ten rabbits in which development of 2KH was accompanied by increments in plasma renin activity (18 to 31·5 ng h—1 ml—1, sem 3 and 4 respectively; P < 0·01) and plasma prostaglandin E2 (1·2 to 3·4 ng/ml, sem 0·2 and 0·4 respectively; P < 0·05), treatment with indomethacin produced renal failure (plasma creatinine increasing to 7·6 mg/100 ml), oliguria, malignant hypertension (mean blood pressure, 168 mmHg, sem 7·7) and death within 5 days. 5. In 1KH, indomethacin decreased plasma renin activity and plasma prostaglandin E2, but caused increased mean blood pressure (102 to 121 mmHg, sem 4 and 6 respectively; P < 0·01) and decreased renal function (plasma creatinine 0·9 ± 0·04 to 3·5 ± 1 mg/100 ml, sem 0·04 and 1 respectively; P < 0·01). 6. Aggravation of hypertension was conditioned by pre-existing levels of renal function and, to a lesser extent, by plasma renin activities. 7. These results suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.

Enhancement of the Antihypertensive Effect of Hydrochlorothiazide in Dogs after Suppression of Renin Release by Beta-Adrenergic Blockade

1975 ◽  
Vol 48 (2) ◽  
pp. 147-151
Author(s):  
C. S. Sweet ◽  
M. Mandradjieff
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Arterial Blood Pressure ◽  
Antihypertensive Effect ◽  
Plasma Renin ◽  
Renin Activity ◽  
Renin Release ◽  
Antihypertensive Activity ◽  
Adrenergic Blockade ◽  
Arterial Blood

1. Renal hypertensive dogs were treated with hydrochlorothiazide (8−2 μmol/kg or 33 μmol/kg daily for 7 days), or timolol (4.6 μmol/kg daily for 4 days), a potent β-adrenergic blocking agent, or combinations of these drugs). Changes in mean arterial blood pressure and plasma renin activity were measured over the treatment period. 2. Neither drug significantly lowered arterial blood pressure when administered alone. Plasma renin activity, which did not change during treatment with timolol, was substantially elevated during treatment with hydrochlorothiazide. 3. When timolol was administered concomitantly with hydrochlorothiazide, plasma renin activity was suppressed and blood pressure was significantly lowered. 4. These observations suggest that compensatory activation of the renin-angiotensin system limits the antihypertensive activity of hydrochlorothiazide in renal hypertensive dogs and suppression of diuretic-induced renin release by timolol unmasks the antihypertensive effect of the diuretic.

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